Risk Factors for Local Failure Following Chemoradiation and Magnetic Resonance Image–Guided Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study
Authors: Maximilian P. Schmid, Jacob C. Lindegaard, Umesh Mahantshetty, Kari Tanderup, Ina Jürgenliemk-Schulz, Christine Haie-Meder, Lars U. Fokdal, Alina Sturdza, Peter Hoskin, Barbara Segedin, Kjersti Bruheim, Fleur Huang, Bhavana Rai, Rachel Cooper, Elzbieta van der Steen-Banasik, Erik Van Limbergen, Bradley R. Pieters, Primoz Petric, Dariga Ramazanova, Robin Ristl, Sadhana Kannan, Rohini Hawaldar, Stefan Ecker, Kathrin Kirchheiner, Li Tee Tan, Remi Nout, Nicole Nesvacil, Astrid de Leeuw, Richard Pötter, Christian Kirisits, Ina Maria Jurgenliemk-Schulz, Fleur Huang, Melissa Christiaens, Hilde Janssen, Marit Sundset, Ludy C.H.W. Lutgens, Elena Villafranca, Janaki Hadjiev, Francois Bachand, Beth Erickson, Geraldine Jacobson, Maarit Anttila, Isabelle Dumas, Gerry Lowe, Jamema Swamidas, Robert Hudej, Taran Paulsen Hellebust, Geetha Menon, Arun S. Oinam, Peter Bownes, Marisol De Brabandere, Bernard Oosterveld, Kees Koedooder, Anne Beate Langeland Marthinsen, Diane Whitney, Martijn Ketelaars, Brigitte Reiniers, Itxa Mora, Gergely Antal, Deidre Batchelar, Jason Rownd, Yusung Kim, Jan-Erik Palmgren, Renaud Mazeron, Cyrus Chargari, Sofia Spampinato
Journal: Journal of Clinical Oncology (2023)

PURPOSE To report clinical and treatment characteristics, remission and failure patterns, and risk factors for local failure (LF) from the EMBRACE-I study. MATERIALS AND METHODS EMBRACE-I was a prospective, observational, multicenter cohort study on magnetic resonance imaging–based image-guided adaptive brachytherapy (MR-IGABT) in locally advanced cervical cancer. Treatment consisted of external beam radiotherapy, concurrent chemotherapy, and MR-IGABT. LF was defined as progressive or recurrent disease in the cervix, uterus, parametria, pelvic wall, or vagina. Competing risk analysis was used to estimate local tumor control (LC) and Cox proportional regression models for multivariable analysis and dose-response analysis. RESULTS One thousand three hundred eighteen patients with a median follow-up of 52 months were available for this analysis. Eighty-one patients had persistent disease 3 months after end of treatment. Of those, 60 patients achieved LC at 6-9 months without further treatment, whereas 21 patients had progressive disease. In addition, 77 patients developed a local recurrence after complete remission comprising a total number of 98 LFs. LFs were located inside the MR-IGABT target volumes in 90% of patients with LF. In multivariable analysis, histology, minimal dose to 90% of high-risk clinical target volume (CTV HR ), maximum tumor dimension, CTV HR &gt; 45 cm 3 , overall treatment time, tumor necrosis on magnetic resonance imaging at diagnosis, uterine corpus infiltration at diagnosis and at MR-IGABT, and mesorectal infiltration at MR-IGABT had significant impact on LF. Dose-response analysis showed that a minimal dose to 90% of 85 Gy to the CTV HR led to 95% (95% CI, 94 to 97) LC 3 years postintervention for squamous cell in comparison to 86% (95% CI, 81 to 90) for adeno/adenosquamous carcinoma histology. CONCLUSION The present study demonstrates the safety and validity of the GYN GEC-ESTRO/ICRU-89 target concept and provides large-scale evidence for dose prescription and new risk factors for LF in MR-IGABT in locally advanced cervical cancer.